This application claims the benefit of priority to U.S. Provisional Patent Application Ser. No. 60/703,042, filed Jul. 27, 2005, which has the same title and inventors as the present application, and is hereby incorporated herein by reference in its entirety.
A. Field of the Invention
The present invention relates generally to methods and compositions for the treatment of actinic keratoses. In particular, the present invention is directed towards compositions comprising calcium channel blocking compounds and related methods for their use in treating and/or preventing actinic keratoses.
B. Background of the Invention
Actinic keratoses (AK), also known as solar keratoses, have been considered to be premalignant skin tumors, but are now increasingly viewed as de facto intraepidermal squamal cell carcinomas (Heaphy and Ackerman, 2000; Ackerman, 2001; Lober and Fenske, 2004). Early AK lesions present as patches with the texture of sandpaper or scabs, with the lesions becoming more discrete as they progress due to hyperkeratosis. The lesions also may become erythematous. AK occur predominantly on sun-exposed areas of fair skinned people, and it has been estimated that 60% of predisposed persons older than 40 years of age have at least one actinic keratosis (Frost and Green, 1994; Salasche, 2000). Patients with AK have an increased incidence of developing new AK, making AK a potentially lifelong condition (Frost and Green, 1994).
Surgical treatments such as cryotherapy, excision and laser resurfacing, while effective against discrete lesions, may not address subclinical lesions, and are painful and associated with risks of scarring, infection and pigmentary changes (Jorizzo et al., 2004; Lober and Fenske, 2004). Many AK patients have multiple lesions, not all of which are discrete and obvious. Suggested treatments for such patients include therapeutic options that treat the entire affected area of skin such as topical treatments and photodynamic therapy. Topical treatment, such as 5-fluouracil, imiquimod, and dicolfenac, however, are less effective that surgical options against discrete lesions and have been associated with irritation, allergic reactions, and problems with patient compliance (Jeffes and Tang, 2000; Topical Diclofenac, 2004; Lober and Fenske, 2004). Photodynamic therapy with aminolevulinic acid is approved in the USA for the treatment of AK. Disadvantages of this therapeutic modality include burning, stinging, cost, and an inconvenient treatment schedule wherein the patient must return to the physician within hours of application of the aminolevulinic acid (Lober and Fenske, 2004).
There is a need for products and methods for the effective treatment of AK, preferably that are convenient to use and obviate such side effects as pain, scarring, and irritation.